Explore the vast range of titles available.

Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8–28·8) in the cilengitide group and 26·3 months (23·9–34·7) in the control group (hazard ratio 1·02, 95% CI 0·81–1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. Merck KGaA, Darmstadt, Germany.

Intraventricular hemorrhage (IVH) occurs in approximately 30–50% patients with spontaneous intracerebral hemorrhage (ICH), with a high 30-day mortality rate. Excess accumulation of parenchymal or ventricular blood associated with the development of acute hydrocephalus leads to poor outcomes. The prediction of shunt dependency is important to identify patients susceptible to requiring permanent shunt placement and benefit from the diversion. This retrospective analytical study aimed to establish a predictive model of shunt dependency in patients with IVH. This study included 179 patients with primary IVH with supratentorial origin or spontaneous ICH with extension into the ventricles between 2015 and 2021. Patients were grouped into “shunt required” and “shunt not required” groups. Variables, including age, sex, preexisting hypertension and diabetes, initial Glasgow Coma Scale scores, ICH location and volume, urokinase administration, modified Graeb score (mGraeb score), and bicaudate index, were analyzed. The shunt required group had significantly higher mGraeb scores (12.0 (6.5–15.0) vs. 7.0 (4.0–12.0), p  = 0.001) and higher bicaudate index (0.20 (0.17–0.23) vs. 0.16 (0.13–0.18), P  < 0.001) than the shunt not required group. The receiver operating characteristic curve (ROC curve) analysis revealed that a cut-off value of 0.16 of the bicaudate index was significantly related to shunt dependency. The subgroup statistical analysis revealed that neither urokinase administration ( p  = 0.533) nor urokinase dosage ( p  = 0.117) showed significant relevance in shunt dependency in patients who received external ventricular drainage. In logistic regression adjusted for the confounders, thalamic ICH (odds ratio (OR) 3.55; 95% confidence interval [(95%CI), 1.13–11.18], an mGraeb score greater than 8 (OR, 3.93; 95%CI, 1.84–8.38), and a bicaudate index greater than 0.16 (OR, 9.87; 95%CI, 3.79–25.73) were factors associated with a higher tendency for shunting. The findings of this study may help identify patients at risk for a permanent shunt after IVH.

Cerebral venous sinus thrombosis (CVST) is a rare cause of cerebral infarction. Once patients survive the acute phase, long-term prognosis is generally satisfactory. CVST patients who harbored risk factors known for poor prognosis (e.g., deterioration of consciousness/neurological functions and seizures) were oftentimes unresponsive to systemic heparin treatment. The advantage of combined endovascular mechanical thrombectomy (EMT) and on-site chemical thrombolysis (OCT) plus systemic heparin for CVST over the heparin treatment alone has not been proved. A retrospective study was conducted to analyze consecutive patients with CVST from 2005 to 2015. Patients having clinical improvement or stable disease after heparin treatment were in I/S group; patients having continuous deterioration of consciousness/neurological functions and refractory seizures (despite the use of multiple anti-epileptic drugs) after heparin treatment were in D group. EMT and OCT were indicated for patients in D group. Imaging studies and medical records were reviewed for statistical analysis. Safety issues included new-onset/progression of symptomatic intracerebral hemorrhages (ICH) or procedure-related complications. Total thirty patients were included (I/S group = 16; D group = 14). In D group, the mean time frame from the start of heparin treatment to the endovascular treatment was 3.2 days. Compared with I/S group, all patients in D group had complete stenosis of the sinuses, with higher initial mRS, lower initial GCS, and more seizures (p = 0.006, 0.007, and 0.031, respectively), but no significant differences in the mRS at discharge (p = 0.504). Shorter length of thrombosis and lower initial mRS were associated with better outcomes (p = 0.009 and 0.003, respectively). Thrombosis involving the superior sagittal sinus (SSS) was associated with bad outcomes (p = 0.026). There were two patients (6.7%) with worsening symptomatic ICH, one in each group, managed surgically. The overall mortality of the study was 6.7% (2/30). Combined EMT and OCT after heparin treatment for severe CVST were reasonably safe, which might be considered as a salvage treatment in severe CVST patients who are unresponsive to heparin with heavy clot burden involving SSS in the acute phase. However, further studies are needed to confirm its efficacy and validity.

Background and Objectives: Pediatric cerebral arteriovenous malformations (AVMs) are associated with significant morbidity and mortality. The aim of this study was to assess the long-term outcomes of surgical excision and stereotactic radiosurgery (SRS) of cerebral AVMs in pediatric patients. Materials and Methods: A single-center retrospective analysis was conducted using data obtained from a single medical center between January 2012 and July 2022. The Modified Rankin Scale (mRS) at admission and discharge and the Spetzler–Martin (SM) scores were analyzed. Results: Among 45 patients (mean age 11.8 years), 19 patients (42.2%) received surgical resection, with good outcomes (mRS 0–2) in 16 patients and complete obliteration in all patients. In total, 26 patients (57.8%) were managed with SRS. After 36.3 months on average, complete obliteration in 19 of 26 patients (69.2%) was confirmed. Among the 7 SRS patients without complete obliteration, 6 had residual cerebral AVMs at the last follow-up, and 1 had recurrence. All patients receiving SRS had favorable outcomes (mRS 0–1) and no apparent radiosurgery-related complications. Conclusions: In our study, the surgical resection or SRS was selected based on individual patient conditions, and the overall outcomes were satisfactory. Both surgical resection and SRS proved to be effective treatment options. Microsurgical resection demonstrated a high rate of obliteration and remains a favorable therapeutic choice with acceptable risks for pediatric AVMs.

Background and Objectives: Recent advancements in spinal navigation methodologies, particularly augmented reality (AR) techniques, have significantly enhanced the precision of spinal instrumentation procedures. This study aimed to evaluate the efficacy of AR-assisted navigation in spinal instrumentation surgery for thoracolumbar scoliosis. Materials and Methods: This retrospective observational study included 10 patients with thoracolumbar scoliosis who met specific inclusion criteria and were recruited at a single medical center. Two neurosurgeons and one neuroradiologist used the Gertzbein–Robbins scale (GRS) for radiological evaluation. Preoperative and postoperative Cobb angles were measured to assess the correction of scoliosis. Overall, 257 screws were placed using the AR-assisted navigation system during thoracic and lumbar spinal deformity surgeries. Results: Among the 257 screws, 197 were placed in the thoracic spine and 60 in the lumbar spine, achieving an overall instrumentation accuracy of 98%. The preoperative Cobb angle of 69.5 ± 22.2° significantly improved to 10.1 ± 4.1° postoperatively. Regarding first-attempt screw placement accuracy, 97.4% of the screws in the thoracic spine (graded as GRS A or B) and 100% in the lumbar spine were placed with precision. Five grade C thoracic screws were identified, one of which required re-instrumentation. Conclusions: The AR navigation technique substantially improved the precision of spinal deformity surgery, with a high screw placement accuracy rate and significant scoliosis correction. The benefits of reduced attention diversion and an intuitive surgical experience suggest that AR technology could significantly improve spinal surgery practices and training programs, indicating potential for broader applicability in the future.

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Background The treatment of large arteriovenous malformations (AVMs), in particular those unruptured, remains a topic of debate. Stereotactic radiosurgery has favorable outcomes for small to medium-sized AVMs. However, for large AVMs, the goal is to maximize obliteration rates and at the same time, to minimize radiation-induced complications. This study assessed outcomes of large symptomatic AVMs treated with Gamma Knife radiosurgery (GKRS) focusing on cases presenting with rupture or seizures. The study followed the guidelines of Taiwan Neurosurgical Consensus, a government-funded committee under the Central Bureau of Health Insurance that determines whether radiosurgery is an appropriate treatment. Materials and methods This retrospective study included 75 cases of large AVMs (> 10 cc) treated with GKRS during the period from June 2003 to January 2020. Inclusion criteria were as follows: a history of intracerebral hemorrhage (ICH) or seizures, no prior embolization, and periodic MRI examinations with clinical assessments post-GKRS. Treatment procedures were adapted based on the Taiwan Neurosurgical Consensus guidelines. Results The average patient age was 36.4 ± 16.1 years, with a median follow-up duration of 104 (range 82–150) months. Forty-six patients (61.3%) underwent single-stage treatment, while 29 patients (38.7%) received two-stage treatment. The mean AVM volume was 20.5 ± 11.7 cc, with an average peripheral radiation dose of 17.7 ± 1.2 Gy. Among the 32 cases with AVM volumes between 10 and 15 cc, 25 (78.1%) achieved total obliteration. For the 17 cases with volumes between 15 and 20 cc, 7 (41.2%) achieved total obliteration, while 8 out of 26 (30.8%) cases with volumes > 20 cc achieved total obliteration. Severe brain edema developed in 16 patients (21.3%) after an average follow-up of 105.4 ± 56.2 months, but 11 patients (14.6%) experienced symptoms. Only one patient (1.3%) suffered neurological disability. Seizure control in Engel classification I was achieved in 21 of 42 patients (50%). Eight patients (10.6%) experienced new hemorrhages, with 4 (12.1%) occurring in those with a prior history of hemorrhage (annual bleeding rate: 1.2%) and 4 (9.5%) in those patients with a history of seizures (annual bleeding rate: 1.1%). Univariate analyses showed that total obliteration was significantly associated with smaller nidus volumes (< 15 cc), single-stage radiosurgery, Radiosurgery-Based Grading Scale, first-stage volume, maximum dose, 12 Gy volume, and nidus coverage percentages at 16 Gy and 18 Gy. Multivariate analyses revealed that post-GKRS symptoms and severe brain edema were significantly correlated with the following: Virginia Radiosurgery AVM Score, Charlson Comorbidity Index, and mean radiation dose. Conclusion The obliteration rate of large AVMs is strongly correlated with their size. This approach appears to achieve the goals of obliteration and minimizing the risks of radiation-induced complications and hemorrhage. Further investigation is needed for adjuvant treatments in residual or refractory cases after GKRS.

IntroductionGlioma surgery near the functional area is still a dilemma. Intraoperative neurophysiologic monitoring (IONM) and functional mapping can play a role to maximize the extent of resection (EOR), while minimizing the risk of sequelae. We herein review the utility of tailored intraoperative mapping and monitoring in patients undergoing glioma surgery in our institute.MethodsPatients were divided into two groups on the basis of application tailored IONM (group A, 2013–2017, n = 53) or not (group B, 2008–2012, n = 49) between January 2008 and December 2017. The setup, tailored IONM protocols, surgery, and clinical results of all patients with eloquent glioma were analyzed with the EOR, functionality scores, overall survival (OS) and progression-free survival (PFS) retrospectively.ResultsThe 102 patients were considered eligible for analysis. High grade and low grade gliomas accounted for 73 (72%) and 29 (28%) cases, respectively. There was a positive association between the application of neuromonitor and post-operative functional preservation, but no significant statistical differences over the EOR, OS and PFS between the two groups.ConclusionsIn our experience, tailored intraoperative functional mapping provides an effective neurological function preservation. Routine implementation of neurophysiological monitoring with adequate pre-operative planning and intraoperative teamwork in eloquent glioma can get more satisfied functional preservation. Due to the maturation and experience of our IONM team may also be the variation factor, prospective studies with a more prominent sample and proper multivariate analysis will be expected to determine the real benefit.

Background The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regression of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment. Methods From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11–12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life. Results The median age of the patients was 48 (15–85) years with median follow up of 77 (26–180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre-SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty-seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion ( p  < 0.05) and deep seated location of the cavernoma ( p  < 0.01). New neurological deficits were highly correlated with decreased mental ( p  < 0.001) and physical ( p  < 0.05) components of quality of life testing, KPS ( p  < 0.001), deep seated location ( p  < 0.01), and increased nidus volume ( p  < 0.05). Quality of life deterioration either in physical component ( p  < 0.01), mental component ( p  < 0.01), and KPS ( p  < 0.05) was highly correlated with increased cavernoma volume. Conclusion Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect.

Glioblastoma multiforme (GBM) is the most aggressive and common primary brain tumor. Magnetic resonance imaging (MRI) provides detailed visualization of tumor morphology, edema, and necrosis. However, manually segmenting GBM from MRI scans is time-consuming, subjective, and prone to inter-observer variability. Therefore, automated and reliable segmentation methods are crucial for improving diagnostic accuracy. This study employs an image semantic segmentation model to segment brain tumors in MRI scans of GBM patients. The MRI recall images include T1-weighted imaging (T1WI) and fluid-attenuated inversion recovery (FLAIR) sequences. To enhance the performance of the semantic segmentation model, image preprocessing techniques were applied before analyzing and comparing commonly used segmentation models. Additionally, a survival model was constructed using discrete genotype attributes of GBM patients. The results indicate that the DeepLabV3+ model achieved the highest accuracy for semantic segmentation, with an accuracy of 77.9% on T1WI image sequences, while the U-Net model achieved 80.1% accuracy on FLAIR image sequences. Furthermore, in constructing the survival model using a discrete attribute dataset, the dataset was divided into three subsets based on different missing value handling strategies. This study found that replacing missing values with 1 resulted in the highest accuracy, with the Bernoulli Bayesian model and the multinomial Bayesian model achieving an accuracy of 94.74%. This study integrates image preprocessing techniques and semantic segmentation models to improve the accuracy and efficiency of brain tumor segmentation while also developing a highly accurate survival model. The findings aim to assist physicians in saving time and facilitating preliminary diagnosis and analysis.